Bottom Line:
Specifically, we examined the possible changes in the subiculum and CA1, regions that seem to be critical for the development and/or maintenance of seizures in these patients.We found a remarkable decrease in synaptic and neuronal density in the sclerotic CA1, and while the subiculum from the sclerotic hippocampus did not display changes in synaptic density, the neuronal density was higher.Since the subiculum from the sclerotic hippocampus displays a significant increase in neuronal density, as well as a various other neurochemical changes, we propose that the apparently normal subiculum from the sclerotic hippocampus suffers profound alterations in neuronal circuits at both the molecular and synaptic level that are likely to be critical for the development or maintenance of seizure activity.

ABSTRACTHippocampal sclerosis is the most frequent pathology encountered in resected mesial temporal structures from patients with intractable temporal lobe epilepsy (TLE). Here, we have used stereological methods to compare the overall density of synapses and neurons between non-sclerotic and sclerotic hippocampal tissue obtained by surgical resection from patients with TLE. Specifically, we examined the possible changes in the subiculum and CA1, regions that seem to be critical for the development and/or maintenance of seizures in these patients. We found a remarkable decrease in synaptic and neuronal density in the sclerotic CA1, and while the subiculum from the sclerotic hippocampus did not display changes in synaptic density, the neuronal density was higher. Since the subiculum from the sclerotic hippocampus displays a significant increase in neuronal density, as well as a various other neurochemical changes, we propose that the apparently normal subiculum from the sclerotic hippocampus suffers profound alterations in neuronal circuits at both the molecular and synaptic level that are likely to be critical for the development or maintenance of seizure activity.

Figure 3: (A) Photomicrograph of a semithin section (2 μm) stained with 1% toluidine blue, showing the pyramidal cell layer of the subiculum from a non-sclerotic hippocampus to illustrate the Cavalieri method used to estimate the Vv. A grid of small intersections overlying the tissue is displayed. Each grid point has an associated area of 20 × 20 = 400 μm2. In this example, the total area of the image is 78,000 μm2. Yellow asterisks indicate the intersections in the grid that lies within cell bodies (n = 25, 25 × 400 = 10,000 μm2). Red asterisks indicate the intersections in the grid that lies within blood vessels (n = 1, 1 × 400 = 400 μm2). The Vv of cells, blood vessels, and neuropil was estimated with the following formulae: Vv cells = 12.8%, Vv blood vessels = 0.51%, Vv neuropil = 100 − (12.8 + 0.51) = 86.7%. (B) Graph of the volume fraction occupied by neuropil, cells bodies, and blood vessels in the pyramidal cell layer of the subiculum from non-sclerotic and sclerotic hippocampus (see text for details).

Mentions:
The estimation of the Vv occupied by the neuropil in the subiculum from sclerotic hippocampus (75%) was lower than in the subiculum from non-sclerotic hippocampus (81%; P < 0.01, Figure 3). In addition, the Vv occupied by cell bodies in the subiculum from the sclerotic hippocampus (21%) was higher than in the non-sclerotic hippocampus (17%; P < 0.01, Figure 3). Thus, the higher neuronal density in the subiculum from the sclerotic hippocampus was consistent with the finding that the Vv occupied by cell bodies in this region was also larger.

Figure 3: (A) Photomicrograph of a semithin section (2 μm) stained with 1% toluidine blue, showing the pyramidal cell layer of the subiculum from a non-sclerotic hippocampus to illustrate the Cavalieri method used to estimate the Vv. A grid of small intersections overlying the tissue is displayed. Each grid point has an associated area of 20 × 20 = 400 μm2. In this example, the total area of the image is 78,000 μm2. Yellow asterisks indicate the intersections in the grid that lies within cell bodies (n = 25, 25 × 400 = 10,000 μm2). Red asterisks indicate the intersections in the grid that lies within blood vessels (n = 1, 1 × 400 = 400 μm2). The Vv of cells, blood vessels, and neuropil was estimated with the following formulae: Vv cells = 12.8%, Vv blood vessels = 0.51%, Vv neuropil = 100 − (12.8 + 0.51) = 86.7%. (B) Graph of the volume fraction occupied by neuropil, cells bodies, and blood vessels in the pyramidal cell layer of the subiculum from non-sclerotic and sclerotic hippocampus (see text for details).

Mentions:
The estimation of the Vv occupied by the neuropil in the subiculum from sclerotic hippocampus (75%) was lower than in the subiculum from non-sclerotic hippocampus (81%; P < 0.01, Figure 3). In addition, the Vv occupied by cell bodies in the subiculum from the sclerotic hippocampus (21%) was higher than in the non-sclerotic hippocampus (17%; P < 0.01, Figure 3). Thus, the higher neuronal density in the subiculum from the sclerotic hippocampus was consistent with the finding that the Vv occupied by cell bodies in this region was also larger.

Bottom Line:
Specifically, we examined the possible changes in the subiculum and CA1, regions that seem to be critical for the development and/or maintenance of seizures in these patients.We found a remarkable decrease in synaptic and neuronal density in the sclerotic CA1, and while the subiculum from the sclerotic hippocampus did not display changes in synaptic density, the neuronal density was higher.Since the subiculum from the sclerotic hippocampus displays a significant increase in neuronal density, as well as a various other neurochemical changes, we propose that the apparently normal subiculum from the sclerotic hippocampus suffers profound alterations in neuronal circuits at both the molecular and synaptic level that are likely to be critical for the development or maintenance of seizure activity.

ABSTRACTHippocampal sclerosis is the most frequent pathology encountered in resected mesial temporal structures from patients with intractable temporal lobe epilepsy (TLE). Here, we have used stereological methods to compare the overall density of synapses and neurons between non-sclerotic and sclerotic hippocampal tissue obtained by surgical resection from patients with TLE. Specifically, we examined the possible changes in the subiculum and CA1, regions that seem to be critical for the development and/or maintenance of seizures in these patients. We found a remarkable decrease in synaptic and neuronal density in the sclerotic CA1, and while the subiculum from the sclerotic hippocampus did not display changes in synaptic density, the neuronal density was higher. Since the subiculum from the sclerotic hippocampus displays a significant increase in neuronal density, as well as a various other neurochemical changes, we propose that the apparently normal subiculum from the sclerotic hippocampus suffers profound alterations in neuronal circuits at both the molecular and synaptic level that are likely to be critical for the development or maintenance of seizure activity.